It is known in the art that the compounds of the formula (I) can be prepared by acylating the compounds of the formula ##STR3##
(DOS No. 2,557,033, European Patent Application No. 51,467). This reaction cannot be considered as a simple acylation. The starting materials as well as the target products can suffer decomposition and the rate of these undesired side-reactions highly depends on the quality and the quantity of the other substances being present in the mixture. E.g. in the presence of acids and bases the compounds undergo trans-cyclization, a 3,6-anhydro ring is formed, the ring can open up, polymerization occurs, etc. The presence of electrolytes, e.g. salts of halogenic acids leads to the formation of the corresponding halogen derivatives. The rate of the decomposition sharply increases with any increase to the temperature.
Due to the undesirable side-reactions a significant portion of the starting materials is transformed into by-products and the amount of the target compound to be prepared is further diminished by the decomposition reactions, therefore the yield of the reaction is highly decreased.
A further problem arises when compounds containing free carboxyl groups are to be prepared by using an acid anhydride as acylating agent. The salt of the monoacyl derivative of the hexitol formed in the first step with the acid binding agent separates from the reaction mixture due to the use of an unsuitable solvent and the diacyl derivative is formed only with poor yields.
When the known processes were attempted on a large scale it was found that they can be reproduced with the reported yields only a laboratory scale (10 millimoles). Using the starting material in an amount of 1,46 kg (10 moles) the 1,2-5,6-dianhydro-3,4-bis(.beta.-carboxypropionyl)-dulcitol could be prepared only with a yield of 4 to 40% instead of 8 to 88%. A further disadvantage of the process is that as .beta.-carbobenzyloxy propionyl chloride is highly susceptible to decomposition, this compound has to be prepared just before the acylation from succinic acid anhydride through succinic acid monobenzylester and this fact further decreases the usability of the process on a large scale.
The object of this invention is to work out a process enabling the industrial scale preparation of the compounds of the formula (I) without using agressive reagents, within short reaction and operation times and at lower temperatures in a reaction medium wherein the monoacyl intermediates comprising free carboxyl groups and the salts of the obtained products with organic bases can be well dissolved.